Discovery of procyanidin condensed tannins of (-)-epicatechin from Kratom, Mitragyna speciosa, as virucidal agents against SARS-CoV-2

Int J Biol Macromol. 2024 Jul;273(Pt 1):133059. doi: 10.1016/j.ijbiomac.2024.133059. Epub 2024 Jun 10.

Abstract

Kratom, Mitragyna speciosa, is one of the most popular herbs in the West and Southeast Asia. A number of previous works have focused on bioactive alkaloids in this plant; however, non-alkaloids have never been investigated for their biological activities. Antiviral and virucidal assays of a methanol leaf extract of Kratom, M. speciosa, revealed that a crude extract displayed virucidal activity against the SARS-CoV-2. Activity-guided isolation of a methanol leaf extract of Kratom led to the identification of B-type procyanidin condensed tannins of (-)-epicatechin as virucidal compounds against SARS-CoV-2. The fraction containing condensed tannins exhibited virucidal activity with an EC50 value of 8.38 μg/mL and a selectivity index (SI) value >23.86. LC-MS/MS analysis and MALDI-TOF MS identified the structure of the virucidal compounds in Kratom as B-type procyanidin condensed tannins, while gel permeation chromatograph (GPC) revealed weight average molecular weight of 238,946 Da for high molecular-weight condensed tannins. In addition to alkaloids, (-)-epicatechin was found as a major component in the leaves of M. speciosa, but it did not have virucidal activity. Macromolecules of (-)-epicatechin, i.e., procyanidin condensed tannins, showed potent virucidal activity against SARS-CoV-2, suggesting that the high molecular weights of these polyphenols are important for virucidal activity.

Keywords: Anti-COVID compounds; COVID-19 control; Polyphenols.

MeSH terms

  • Animals
  • Antiviral Agents* / chemistry
  • Antiviral Agents* / pharmacology
  • Biflavonoids* / chemistry
  • Biflavonoids* / pharmacology
  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • Catechin* / chemistry
  • Catechin* / pharmacology
  • Chlorocebus aethiops
  • Humans
  • Mitragyna* / chemistry
  • Plant Extracts* / chemistry
  • Plant Extracts* / pharmacology
  • Plant Leaves* / chemistry
  • Proanthocyanidins* / chemistry
  • Proanthocyanidins* / pharmacology
  • SARS-CoV-2* / drug effects
  • Tandem Mass Spectrometry
  • Vero Cells

Substances

  • Catechin
  • Proanthocyanidins
  • Antiviral Agents
  • Plant Extracts
  • Biflavonoids
  • procyanidin